Lassa fever and rabies vaccine shows promise in animal testing

A novel vaccine designed to protect people from both Lassa fever and rabies showed promise in preclinical testing, according to new research published in Nature Communications. The investigational vaccine, called LASSARAB, was developed and tested by scientists at Thomas Jefferson University in Philadelphia; the University of Minho in Braga, Portugal; the University of California, San Diego; and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Image/C. S. Goldsmith, P. Rollin, M. BowenThis transmission electron micrograph (TEM) depicted numbers of Lassa virus virions adjacent to some cell debris. The virus, a member of the virus family Arenaviridae, is a single-stranded RNA virus, and is zoonotic, or animal-borne that can be transmitted to humans. The illness, which occurs in West Africa, was discovered in 1969 when two missionary nurses died in Nigeria, West Africa.In areas of Africa where the disease is endemic (that is, constantly present), Lassa fever is a significant cause of morbidity and mortality. While Lassa fever is mild or has no observable symptoms in about 80% of people infected with the virus, the remaining 20% have a severe multisystem disease. Lassa fever is also associated with occasional epidemics, during which the case-fatality rate can reach 50%.There are a number of ways in which the virus may be transmitted, or spread, to humans. The Mastomys rodents shed the virus in urine and droppings. Therefore, the virus can be transmitted through direct contact with these materials, through touching objects or eating food contaminated with these materials, or through cuts or sores. Because Mastomys rodents often live in and around homes and scavenge on human food remains or poorly stored food, transmission of this sort is common. Contact with the virus also may occur when a person inhales tiny particles in the air contaminated with rodent excretions. This is called aerosol or airborne transmission. Finally, because Mastomys rodents are sometimes consumed as a food source, infection may occur via direct contact when they are caught and prepared for food.

The inactivated recombinant vaccine candidate uses a weakened rabies virus vector, or carrier. The research team inserted genetic material from Lassa virus into the rabies virus vector so the vaccine expresses surface proteins from both the Lassa virus and the rabies virus. These surface proteins prompt an immune response against both Lassa and rabies viruses. The recombinant vaccine was then inactivated to “kill” the live rabies virus used to make the carrier.

There are currently no approved Lassa fever vaccines. Although Lassa fever is often a mild illness, some people experience serious symptoms, such as hemorrhage (severe bleeding) and shock. The overall Lassa virus infection case-fatality rate is about 1 percent, according to the World Health Organization (WHO), but that rate rises to 15 percent for patients hospitalized with severe cases of Lassa fever. People contract Lassa virus through contact with infected Mastomys rats and through exposure to an infected person’s bodily fluids. Lassa fever is endemic to West Africa where these rats are common. In 2018, Nigeria experienced its largest-ever Lassa fever outbreak, with 514 confirmed cases and 134 deaths from Jan. 1 through Sept. 30, according to the Nigeria Centre for Disease Control.

Africa is also at high risk for human rabies. The WHO estimates that 95 percent of the estimated 59,000 human rabies deaths per year occur in Africa and Asia (link is external). Nearly all human rabies deaths are caused by bites or scratches from infected dogs. Effective rabies vaccines and post-exposure shots are available, but many deaths still occur in resource-limited countries, according to the Centers for Disease Control and Prevention.

The newly published findings show that LASSARAB, when administered with GLA-SE adjuvant (an immune response-stimulating protein), elicits antibodies against Lassa virus and rabies virus in mouse and guinea pig models. The vaccine also protected guinea pigs from Lassa fever after being exposed to the virus 58 days after vaccination.

Prior research indicated that an antibody-mediated immune response is not correlated with protection from Lassa fever, the authors note. However, the new findings show that high levels of non-neutralizing immunoglobulin G (IgG) antibodies that bind to the Lassa virus surface protein correlate with protection against Lassa virus. Levels of this type of antibody could potentially be a Lassa fever correlate of protection used to determine vaccine efficacy, according to the authors. They note the next step is to evaluate the experimental vaccine in nonhuman primates before advancing to human clinical trials.

You can find out more about which cookies we are using or switch them off in settings.

Privacy Overview

This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.

You can adjust all of your cookie settings by navigating the tabs on the left hand side.

Strictly Necessary Cookies

Strictly Necessary Cookie should be enabled at all times so that we can save your preferences for cookie settings.

disable

If you disable this cookie, we will not be able to save your preferences. This means that every time you visit this website you will need to enable or disable cookies again.